反应详情

温度

50 °C

4-Methylbenzenesulfonohydrazide (0.177 g, 0.948 mmol) in MeOH (4 mL) was combined with (4-fluorophenyl)((7aR,11aS)-11a-(pyridin-2-ylmethyl)-5,6,7,7a,8,10,11,11a-octahydrospiro[benzo[6,7]cyclohepta[1,2-c]pyridine-9,2′-[1,3]dioxolan]-3-yl)methanone (0.224 g, 0.474 mmol) and the mixture was stirred at about 50° C. for about 48 h. The reaction mixture was cooled to rt and was washed with sat. aq. NaHCO3 and extracted with DCM (10 mL). The organics were dried over MgSO4 and concentrated in vacuo. The residue was purified on silica gel (12 g) using a gradient of 10-100% EtOAc in heptane to afford (4aR,13bS)-9-(4-fluorophenyl)-13b-(pyridin-2-ylmethyl)-1,2,4,4a,5,6,7,13b-octahydrospiro[benzo[3,4]cyclohepta[1,2-d][1,2,3]triazolo[1,5-a]pyridine-3,2′-[1,3]dioxolane] (156, R1=4-Fluorophenyl, R2=Pyridin-2-ylmethyl) (0.230 g, 56%); LC/MS, method 3, Rt=2.52 min, MS m/z 485 (M+H)+. 1H NMR (400 MHz, DMSO) δ 8.36 (s, 1H), 8.28-8.23 (m, 1H), 8.10-8.02 (m, 3H), 7.80-7.72 (m, 1H), 7.41-7.30 (m, 2H), 7.02-6.97 (m, 1H), 6.57-6.53 (m, 1H), 3.96-3.80 (m, 4H), 3.63-3.54 (m, 1H), 3.52-3.40 (m, 1H), 3.25-3.17 (m, 2H), 2.39-2.34 (m, 1H), 2.21-2.05 (m, 2H), 1.95-1.55 (m, 7H), 1.50-1.37 (m, 1H)

1. temperatureThe reaction mixture was cooled to rt
2. washwas washed with sat. aq. NaHCO3
3. extractionextracted with DCM (10 mL)
4. dry with materialThe organics were dried over MgSO4
5. concentrationconcentrated in vacuo
6. customThe residue was purified on silica gel (12 g)